Phenylethanolamine N-methyltranferase (PNMT) is the enzyme that catalyzes the conversion of norepinephrine into epinephrine. Increased levels of this enzyme are found during periods of stress and in hypertensive animals. A series of nonaromatic analogs of phenylethanolamine are proposed for synthesis. These compounds will be evaduated as substrates and alternate substrate inhibitors for PNMT. These results on alternate substrate type inhibitors will afford information on the binding requirements at the enzymes' active site and this information will be used for the design of non-aromatic dead end type inhibitors. Potent in vitro inhibitors will be evaluated in vivo for their effect as inhibitors of PNMT and for other adrenergic effects that might limit their usefulness as valuable pharmacological tools or as clinically effective antihypertensive agents. With the exception of our preliminary reports, all other inhibitors of PNMT have contained on aromatic ring which has limited their effectiveness, as pharmacological tools, because of a significant variety of adrenergic side effects. Our preliminary studies have shown that the non-aromatic ring containing ethanolamines have minimal adrenergic effects and thus offer promise for the design of selective inhibitors of PNMT.